tbuckley/cabot-search huggingface dataset:
Prognostic impact of Breslow thickness in acral melanoma: A retrospective analysis
Authors: Xiaoting Wei, Yu Chen, Hong Yao, Di Wu, Hang Li, Rui Zhang, Zhihong Chi, Chuanliang Cui, Xue Bai, Lili Mao, Zhonghui Qi, Ke Li, Shijie Lan, Lizhu Chen, Rui Guo, Xinyu Yao, Bin Lian, Yan Kong, Jie Dai, Bixia Tang, Xuan Wang, Jeffrey E. Gershenwald, Charles M. Balch, Jun Guo, Lu Si
Journal: Journal of the American Academy of Dermatology (2022)

BackgroundEvidence for the prognostic importance of tumor thickness in acral melanoma (AM) patients is limited.ObjectiveThe objective of the study was to determine the prognostic impact of Breslow thickness in AM.MethodsThis multicenter study enrolled patients diagnosed with localized AM between January 1, 2000 and December 31, 2017. Melanoma-specific survival (MSS) in different tumor thickness strata (T1-T4: ≤1, >1-2, >2-4, >4 mm, respectively) was estimated by the Kaplan-Meier method. Comparisons were performed by the log-rank test and multivariable Cox regression.ResultsA total of 853 patients with clinical N0 (cN0) AM were included in the analysis. The median follow-up time was 60.1 months. The median MSS in patients with T1-T4 disease was not reached, 111.0, 92.8, and 67.1 months, respectively. MSS differed significantly among cN0 patients with T1-T3 AM (log-rank P = .004, .012, <0.001 for T1 vs T2, T2 vs T3, and T1 vs T3, respectively); however, there was no significant difference between T3 and T4 AM (hazard ratio = 0.82, 95% CI, 0.62-1.09). Six-subgroup analyses confirmed that survival outcomes were similar between different subgroups with tumor thickness >2 mm.LimitationsThe limitations were retrospective design and some missing variables.ConclusionsThere was no association between tumor thickness and survival in AM patients with a Breslow thickness >2 mm. Evidence for the prognostic importance of tumor thickness in acral melanoma (AM) patients is limited. The objective of the study was to determine the prognostic impact of Breslow thickness in AM. This multicenter study enrolled patients diagnosed with localized AM between January 1, 2000 and December 31, 2017. Melanoma-specific survival (MSS) in different tumor thickness strata (T1-T4: ≤1, >1-2, >2-4, >4 mm, respectively) was estimated by the Kaplan-Meier method. Comparisons were performed by the log-rank test and multivariable Cox regression. A total of 853 patients with clinical N0 (cN0) AM were included in the analysis. The median follow-up time was 60.1 months. The median MSS in patients with T1-T4 disease was not reached, 111.0, 92.8, and 67.1 months, respectively. MSS differed significantly among cN0 patients with T1-T3 AM (log-rank P = .004, .012, <0.001 for T1 vs T2, T2 vs T3, and T1 vs T3, respectively); however, there was no significant difference between T3 and T4 AM (hazard ratio = 0.82, 95% CI, 0.62-1.09). Six-subgroup analyses confirmed that survival outcomes were similar between different subgroups with tumor thickness >2 mm. The limitations were retrospective design and some missing variables. There was no association between tumor thickness and survival in AM patients with a Breslow thickness >2 mm.
The Prevalence of Nosocomial Infection in Intensive Care Units in Europe
Authors: Jean-Louis Vincent
Journal: JAMA (1995)

<h3>Objective.</h3> —To determine the prevalence of intensive care unit (ICU)—acquired infections and the risk factors for these infections, identify the predominant infecting organisms, and evaluate the relationship between ICU-acquired infection and mortality. <h3>Design.</h3> —A 1-day point-prevalence study. <h3>Setting.</h3> —Intensive care units in 17 countries in Western Europe, excluding coronary care units and pediatric and special care infant units. <h3>Patients.</h3> —All patients (&gt;10 years of age) occupying an ICU bed over a 24-hour period. A total of 1417 ICUs provided 10 038 patient case reports. <h3>Main Outcome Measures.</h3> —Rates of ICU-acquired infection, prescription of antimicrobials, resistance patterns of microbiological isolates, and potential risk factors for ICU-acquired infection and death. <h3>Results.</h3> —A total of 4501 patients (44.8%) were infected, and 2064 (20.6%) had ICU-acquired infection. Pneumonia (46.9%), lower respiratory tract infection (17.8%), urinary tract infection (17.6%), and bloodstream infection (12%) were the most frequent types of ICU infection reported. Most frequently reported microorganisms were Enterobacteriaceae (34.4%),<i>Staphylococcus aureus</i>(30.1%; [60% resistant to methicillin]),<i>Pseudomonas aeruginosa</i>(28.7%), coagulase-negative staphylococci (19.1%), and fungi (17.1%). Seven risk factors for ICU-acquired infection were identified: increasing length of ICU stay (&gt;48 hours), mechanical ventilation, diagnosis of trauma, central venous, pulmonary artery, and urinary catheterization, and stress ulcer prophylaxis. ICU-acquired pneumonia (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.6 to 2.29), clinical sepsis (OR, 3.50; 95% CI, 1.71 to 7.18), and bloodstream infection (OR, 1.73; 95% CI, 1.25 to 2.41) increased the risk of ICU death. <h3>Conclusions.</h3> —ICU-acquired infection is common and often associated with microbiological isolates of resistant organisms. The potential effects on outcome emphasize the importance of specific measures for infection control in critically ill patients. (<i>JAMA</i>. 1995;274:639-644)
Relapsing Polychondritis
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Understanding pulse oximetry in hematology patients: Hemoglobinopathies, racial differences, and beyond
Authors: Sarah Patterson, Nick Sandercock, Madeleine Verhovsek
Journal: American Journal of Hematology (2022)

Pulse oximetry (SpO2 ) is a widely used, non-invasive method of estimating arterial oxygen saturation. Measurement of SpO2 relies on comparing the relative absorption of light in the red and infrared regions with the expected absorption pattern of oxygenated and deoxygenation adult hemoglobin. As this screening tool has entered common clinical use, test limitations have emerged, including concern about the risk of overestimation of oxygen saturation by pulse oximetry in a disproportionate number of people with dark skin pigment, leading to potential for underdiagnosis of true hypoxemia. In addition, a range of challenges may arise in patients with increased levels of methemoglobin - whether acquired or inherited - carboxyhemoglobin, or in patients with a subset of inherited variant hemoglobins. It is important for Hematologists, and indeed all clinicians who rely on pulse oximetry, to understand the principles and limitations of this ubiquitous test.
Brain Microenvironment Responsive and Pro‐Angiogenic Extracellular Vesicle‐Hydrogel for Promoting Neurobehavioral Recovery in Type 2 Diabetic Mice After Stroke
Authors: Yixu Jiang, Ruiqi Wang, Cheng Wang, Yiyan Guo, Tongtong Xu, Zhijun Zhang, Guo‐Yuan Yang, He Xu, Yaohui Tang
Journal: Advanced Healthcare Materials (2022)

Stroke patients with diabetes have worse neurological outcomes than non-diabetic stroke patients, and treatments beneficial for non-diabetic stroke patients are not necessarily effective for diabetic stroke patients. While stem cell-derived extracellular vesicles (EVs) show potential for treating stroke, the results remain unsatisfactory due to the lack of approaches for retaining and controlling EVs released into the brain. Herein, a glucose/reactive oxygen species dual-responsive hydrogel showing excellent injectability, biocompatibility, and self-healing capability is introduced as an EVs-loading vehicle and an intelligent EVs sustained releasing system in the brain. These EVs-hydrogels are developed via crosslinking of phenylboronic acid-modified hyaluronic acid and Poly vinyl alcohol, and fusion with neural stem cell-derived EVs. The results show EVs are stably incorporated into the hydrogels and can be controllably released in response to the brain microenvironment after stroke in type 2 diabetic mice. The EVs-hydrogels exert an excellent angiogenic effect, increasing the migration and tube formation of human umbilical vein endothelial cells. In addition, injection of EVs-hydrogels into the ischemic mouse brain enhances EVs retention and facilitates sustained release, promotes angiogenesis, and improves neurobehavioral recovery. These results suggest such a microenvironment responsive and sustained release EVs-hydrogel system offers a safe, and efficient therapy for diabetic stroke.
Attention‐deficit/hyperactivity disorder as a risk factor for cardiovascular diseases: a nationwide population‐based cohort study
Authors: Lin Li, Zheng Chang, Jiangwei Sun, Miguel Garcia‐Argibay, Ebba Du Rietz, Maja Dobrosavljevic, Isabell Brikell, Tomas Jernberg, Marco Solmi, Samuele Cortese, Henrik Larsson
Journal: World Psychiatry (2022)

Accumulating evidence suggests a higher risk for cardiovascular diseases among individuals with mental disorders, but very little is known about the risk for overall and specific groups of cardiovascular diseases in people with attention-deficit/hyperactivity disorder (ADHD). To fill this knowledge gap, we investigated the prospective associations between ADHD and a wide range of cardiovascular diseases in adults. In a nationwide population-based cohort study, we identified 5,389,519 adults born between 1941 and 1983, without pre-existing cardiovascular diseases, from Swedish registers. The study period was from January 1, 2001 to December 31, 2013. Incident cardiovascular disease events were identified according to ICD codes. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression model, with ADHD as a time-varying exposure. After an average 11.80 years of follow-up, 38.05% of individuals with ADHD versus 23.57% of those without ADHD had at least one diagnosis of cardiovascular disease (p<0.0001). ADHD was significantly associated with increased risk of any cardiovascular disease (HR=2.05, 95% CI: 1.98-2.13) after adjusting for sex and year of birth. Further adjustments for education level, birth country, type 2 diabetes mellitus, obesity, dyslipidemia, sleep problems and heavy smoking attenuated the association, which however remained significant (HR=1.84, 95% CI: 1.77-1.91). Further adjustment for psychiatric comorbidities attenuated but could not fully explain the association (HR=1.65, 95% CI: 1.59-1.71). The strongest associations were found for cardiac arrest (HR=2.28, 95% CI: 1.81-2.87), hemorrhagic stroke (HR=2.16, 95% CI: 1.68-2.77), and peripheral vascular disease/arteriosclerosis (HR=2.05, 95% CI: 1.76-2.38). Stronger associations were observed in males and younger adults, while comparable associations were found among individuals with or without psychotropic medications and family history of cardiovascular diseases. These data suggest that ADHD is an independent risk factor for a wide range of cardiovascular diseases. They highlight the importance of carefully monitoring cardiovascular health and developing age-appropriate and individualized strategies to reduce the cardiovascular risk in individuals with ADHD.
Detection of Higher Cycle Threshold Values in Culturable SARS-CoV-2 Omicron BA.1 Sublineage Compared with Pre-Omicron Variant Specimens — San Francisco Bay Area, California, July 2021—March 2022
Authors: Michel Tassetto, Miguel Garcia-Knight, Khamal Anglin, Scott Lu, Amethyst Zhang, Mariela Romero, Jesus Pineda-Ramirez, Ruth Diaz Sanchez, Kevin C. Donohue, Karen Pfister, Curtis Chan, Sharon Saydah, Melissa Briggs-Hagen, Michael J. Peluso, Jeffrey N. Martin, Raul Andino, Claire M. Midgley, J. Daniel Kelly
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Before emergence in late 2021 of the highly transmissible B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19 (1,2), several studies demonstrated that SARS-CoV-2 was unlikely to be cultured from specimens with high cycle threshold (Ct) values
Modeling Biochemical Gradients In Vitro to Control Cell Compartmentalization in a Microengineered 3D Model of the Intestinal Epithelium
Authors: Gizem Altay, Aina Abad‐Lázaro, Emilio J. Gualda, Jordi Folch, Claudia Insa, Sébastien Tosi, Xavier Hernando‐Momblona, Eduard Batlle, Pablo Loza‐Álvarez, Vanesa Fernández‐Majada, Elena Martinez
Journal: Advanced Healthcare Materials (2022)

Gradients of signaling pathways within the intestinal stem cell (ISC) niche are instrumental for cellular compartmentalization and tissue function, yet how are they sensed by the epithelium is still not fully understood. Here a new in vitro model of the small intestine based on primary epithelial cells (i), apically accessible (ii), with native tissue mechanical properties and controlled mesh size (iii), 3D villus-like architecture (iv), and precisely controlled biomolecular gradients of the ISC niche (v) is presented. Biochemical gradients are formed through hydrogel-based scaffolds by free diffusion from a source to a sink chamber. To confirm the establishment of spatiotemporally controlled gradients, light-sheet fluorescence microscopy and in-silico modeling are employed. The ISC niche biochemical gradients coming from the stroma and applied along the villus axis lead to the in vivo-like compartmentalization of the proliferative and differentiated cells, while changing the composition and concentration of the biochemical factors affects the cellular organization along the villus axis. This novel 3D in vitro intestinal model derived from organoids recapitulates both the villus-like architecture and the gradients of ISC biochemical factors, thus opening the possibility to study in vitro the nature of such gradients and the resulting cellular response.
Author Correction: Feasibility of anomaly score detected with deep learning in irradiated breast cancer patients with reconstruction
Authors: Dong-Yun Kim, Soo Jin Lee, Eun-Kyu Kim, Eunyoung Kang, Chan Yeong Heo, Jae Hoon Jeong, Yujin Myung, In Ah Kim, Bum-Sup Jang
Journal: npj Digital Medicine (2022)
The druggable transcription factor Fli-1 regulates T cell immunity and tolerance in graft-versus-host disease
Authors: Steven D. Schutt, Yongxia Wu, Arjun Kharel, David Bastian, Hee-Jin Choi, Mohammed Hanief Sofi, Corey Mealer, Brianyell McDaniel Mims, Hung Nguyen, Chen Liu, Kris Helke, Weiguo Cui, Xian Zhang, Yaacov Ben-David, Xue-Zhong Yu
Journal: Journal of Clinical Investigation (2022)

Graft-versus-host disease (GVHD), manifesting as either acute (aGVHD) or chronic (cGVHD), presents significant life-threatening complications following allogeneic hematopoietic cell transplantation. Here, we investigated Friend virus leukemia integration 1 (Fli-1) in GVHD pathogenesis and validated Fli-1 as a therapeutic target. Using genetic approaches, we found that Fli-1 dynamically regulated different T cell subsets in allogeneic responses and pathogenicity in the development of aGVHD and cGVHD. Compared with homozygous Fli1-deficient or WT T cells, heterozygous Fli1-deficient T cells induced the mildest GVHD, as evidenced by the lowest Th1 and Th17 cell differentiation. Single-cell RNA-Seq analysis revealed that Fli-1 differentially regulated CD4+ and CD8+ T cell responses. Fli-1 promoted the transcription of Th1/Th17 pathways and T cell receptor-inducible (TCR-inducible) transcription factors in CD4+ T cells, while suppressing activation- and function-related gene pathways in CD8+ T cells. Importantly, a low dose of camptothecin, topotecan, or etoposide acted as a potent Fli-1 inhibitor and significantly attenuated GVHD severity, while preserving the graft-versus-leukemia (GVL) effect. This observation was extended to a xenograft model, in which GVHD was induced by human T cells. In conclusion, we provide evidence that Fli-1 plays a crucial role in alloreactive CD4+ T cell activation and differentiation and that targeting Fli-1 may be an attractive strategy for treating GVHD without compromising the GVL effect.
Anti-spike T-cell and Antibody Responses to SARS-CoV-2 mRNA Vaccines in Patients with Hematologic Malignancies
Authors: Lee M. Greenberger, Larry A. Saltzman, Lore M. Gruenbaum, Jun Xu, Sneha T. Reddy, Jonathon W. Senefeld, Patrick W. Johnson, Paul A. Fields, Catherine Sanders, Louis J. DeGennaro, Gwen L. Nichols
Journal: Blood Cancer Discovery (2022)

Abstract The anti-spike T-cell and antibody responses to SARS-CoV-2 mRNA vaccines in patients with B-cell malignancies were examined in a real-world setting. A next-generation sequencing (NGS)–based molecular assay was used to assess SARS-CoV-2–specific T-cell responses. After the second dose, 58% (166/284) of seropositive and 45% (99/221) of seronegative patients display anti-spike T cells. The percentage of patients who displayed T-cell response was higher among patients receiving mRNA-1273 vaccines compared with those receiving BNT162b2 vaccines. After the third vaccination, 40% (137/342) of patients seroconverted, although only 22% displayed sufficient antibody levels associated with the production of neutralizing antibodies. 97% (717/738) of patients who were seropositive before the third dose had markedly elevated anti-spike antibody levels. Anti-spike antibody levels, but not T-cell responses, were depressed by B cell–directed therapies. Vaccinated patients with B-cell malignancies with a poor response to SARS-CoV-2 vaccines may remain vulnerable to COVID-19 infections. Significance: This study represents the first investigation of SARS-CoV-2–specific immune responses to vaccination in a patient registry using an NGS-based method for T-cell receptor repertoire–based analysis combined with anti-spike antibody assessments. Vaccinated patients with B cell–derived hematologic malignancies are likely at higher risk of infection or severe COVID-19. This article is highlighted in the In This Issue feature, p. 476
Biomarkers in heart failure clinical trials. A review from the Biomarkers Working Group of the Heart Failure Association of the European Society of Cardiology
Authors: Antoni Bayes‐Genis, Alberto Aimo, Pardeep Jhund, Mark Richards, Rudolf A. de Boer, Henrike Arfsten, Iacopo Fabiani, Josep Lupón, Stefan D. Anker, Arantxa González, Vincenzo Castiglione, Marco Metra, Christian Mueller, Julio Núñez, Patrick Rossignol, Andrea Barison, Javed Butler, John Teerlink, Gerasimos Filippatos, Piotr Ponikowski, Giuseppe Vergaro, Faiez Zannad, Petar Seferovic, Giuseppe Rosano, Andrew J.S. Coats, Michele Emdin, James L. Januzzi
Journal: European Journal of Heart Failure (2022)
CD200 ectodomain shedding into the tumor microenvironment leads to NK cell dysfunction and apoptosis
Authors: Huw J. Morgan, Elise Rees, Simone Lanfredini, Kate A. Powell, Jasmine Gore, Alex Gibbs, Charlotte Lovatt, Gemma E. Davies, Carlotta Olivero, Boris Y. Shorning, Giusy Tornillo, Alex Tonks, Richard Darley, Eddie C.Y. Wang, Girish K. Patel
Journal: Journal of Clinical Investigation (2022)

The basis of immune evasion, a hallmark of cancer, can differ even when cancers arise from one cell type such as in the human skin keratinocyte carcinomas: basal and squamous cell carcinoma. Here we showed that the basal cell carcinoma tumor-initiating cell surface protein CD200, through ectodomain shedding, was responsible for the near absence of NK cells within the basal cell carcinoma tumor microenvironment. In situ, CD200 underwent ectodomain shedding by metalloproteinases MMP3 and MMP11, which released biologically active soluble CD200 into the basal cell carcinoma microenvironment. CD200 bound its cognate receptor on NK cells to suppress MAPK pathway signaling that in turn blocked indirect (IFN-γ release) and direct cell killing. In addition, reduced ERK phosphorylation relinquished negative regulation of PPARγ-regulated gene transcription and led to membrane accumulation of the Fas/FADD death receptor and its ligand, FasL, which resulted in activation-induced apoptosis. Blocking CD200 inhibition of MAPK or PPARγ signaling restored NK cell survival and tumor cell killing, with relevance to many cancer types. Our results thus uncover a paradigm for CD200 as a potentially novel and targetable NK cell-specific immune checkpoint, which is responsible for NK cell-associated poor outcomes in many cancers.
The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies
Authors: Ruixue Bai, Yunong Li, Lingyan Jian, Yuehui Yang, Lin Zhao, Minjie Wei
Journal: Molecular Cancer (2022)

Abstract Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.